Abstract:

Selection for High Alcohol Preference Drinking in Mice Results
in Heightened Sensitivity and Rapid Development of Acute
Functional Tolerance to Alcohol’s Ataxic Effects
Brandon M. Fritz
,
Nicholas J. Grahame
, and
Stephen L. Boehm II
Indiana Alcohol Research Center and Department of Psychology, Indiana University – Purdue
University Indianapolis, Indianapolis, IN 46202
Abstract
Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may
influence the amount of alcohol consumed, with higher drinking associated with greater acute
functional tolerance (AFT). The goal of the current study was to assess this potential correlated
response between alcohol preference and AFT in second and third replicate lines of mice
selectively bred for high (HAP2&3) and low (LAP2&3) alcohol preference drinking. Male and
female mice were tested for development of AFT on a static dowel task which requires that
animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse
received one (1.75g/kg; Experiment 1) or two (1.75g/kg and 2.0g/kg; Experiment 2) injections of
ethanol; an initial administration before being placed on the dowel and in Experiment 2, an
additional administration after the first regain of balance on the dowel. Blood samples were taken
immediately after loss of balance (when BECs were rising) and at recovery (during falling BECs)
in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice
fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial
injection of ethanol and were therefore more sensitive to its early effects. Furthermore,
Experiment 1 detected significantly greater AFT development (BECfalling - BECrising) in HAP
mice as compared to LAP mice which occurred within ~30 min, supporting our hypothesis.
However, AFT was not different between lines in Experiment 2, indicating that ~30–60 min
following alcohol administration, AFT development was similar in both lines. These data show
that high alcohol drinking genetically associates with both high initial sensitivity and very early
tolerance to the ataxic effects of ethanol.